This application is in response to the CREG announcement entitled, "Experimental Combined Modality (Radiotherapy--Chemotherapy) Studies (ECMRC)," DCT-3, published in NIH Guide for Grants and Contracts, Vol. 7, No. 9, June 30, 1978. The effectiveness of combinations of cytostatic chemotherapeutic drugs with radiation will be determined for several endpoints. Drugs to be used include adriamycin, actinomycin D, cyclophosphamide, BCNU, cis-platinum, and bleomycin. Tumor response will be evaluated by growth delay of 3 tumors, EMT6 sarcoma, RIF-1 sarcoma, and MDAH/MCa4 carcinoma, tested in syngeneic mice; and by clonogenic survival of tumor cells, determined in vitro, for RIF-1 and EMT6 tumors after treatment in vivo. Changes in the fractions of proliferating (P) and non-proliferating (Q) clonogenic tumor cells will be studied in EMT6 and RIF-1 tumors, using the micro-colony 3HTdR labeling method. Combined modality effects will also be studied in the spinal cord, lung, kidney, and skin. Treatment regimens will be evaluated for effects on the spread of lymphatic or blood-borne metastases from footpad-implanted KHT tumors. Cells grown in vitro will be used to test for potentially valuable cytostatic agents other than the 6 drugs listed, and to investigate mechanisms of enhanced effectiveness in combined modality regimens. Intensive investigation will be undertaken of fractionated drug/radiation regimens as well as baseline single dose experiments. Testing in the tumor and normal tissue systems is intended ultimately to provide information about the therapeutic ratio of different combinations of modalities, i.e., the effect of treatment on malignant cells relative to the effects on normal tissues.